Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients after Chemoradiation: Its Clinical Implications

Abstract

Background: We have limited knowledge of the geographic distribution of resistant esophageal adenocarcinoma (EAC) in resected specimens, but its clinical importance can be enormous. Method: We selected patients with baseline stage III EAC who had had chemoradiation followed by surgery and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (percentage of resistant EAC and anatomic distribution). Results: A total of 100 clinical stage III patients were studied; 90% had an R0 resection, and 99% had either moderate or poorly differentiated EAC. Twelve percent had >50% residual cancer, 31% had 11-50% residual cancer, 53% had 1-10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa (66%), muscularis propria (76%), and serosa (62%); all compartments were involved in 35% of the cases. Lack of EAC (meaning response) was observed in the mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery showed no EAC in 79% of the patients, in the surgical specimens, resistant EAC was frequently occurring in the mucosa/submucosa (66%). Conclusion: Contrary to our hypothesis that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the postchemoradiation biopsies are misleading, and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients.

Radiation field size and dose determine oncologic outcome in esophageal cancer

“…Residual tumor within radiation therapy target volume after Def-CRT with the current standard radiation treatment parameters (50.4Gy, 5 cm margins to GTV) is also the most common cause of locoregional failures [ 3 , 4 , 32 , 33 ]. Residual tumor besides causing locoregional failure also results in distant metastases and worsens prognosis [ 28 , 32 – 35 ]. Residual tumor outside CTV borders were identified in 14 % of the patients’ tumor pieces operated after Pre-CRT with a CTV obtained by adding 3.5 cm margins to GTV craniocaudally [ 28 ].…”

Advances in diagnosis and management of cancer of the esophagus

“…The accurate identification of residual or recurrent disease is central to these trials, but concerns have been raised regarding the sensitivity of conventional response assessments. [227][228][229] A recent study showed that the use of bite-on-bite biopsies delivers a 20% improvement in the detection of residual esophageal cancer. 230 A separate study (preSINO) is ongoing, and will determine the accuracy of radiographic and endoscopic evaluation of clinical complete response in squamous cell esophageal cancer.…”

Silencing Glypican-1 enhances the antitumor effects of Pictilisib via downregulating PI3K/Akt/ERK signaling in chemo-resistant esophageal adenocarcinoma

“…Tumor volume was calculated using the formula; tumor volume (mm 3 =/6 × a × b. 2 ) When tumor volumes reached 50 mm 3 mice were randomly divided into four groups (4 mice per group). Group 1: scramble control; Group 2: shGPC-1, Group 3: Scramble control +Pictilisib; Group 4: shGPC-1+ Pictilisib.…”

“…It is often diagnosed in an advanced stage, shows rapid disease progression, frequent resistance to conventional chemotherapy and radiation which results in an extremely poor prognosis. 2 , 3 Despite significant treatment advances the 5-year survival of EAC patients is only 23%. 4 As our understanding of the molecular mechanisms underlying the biology of EAC improves, opportunities to develop novel effective therapies targeted toward improving survival and quality of life in EAC need to be explored.…”